| Abstract: | Levels of the excitotoxin quinolinic acid (QUIN) were measured in the cerebrospinal fluid of infants and children with congenital hyperammonemia. Twofold to tenfold elevations of QUIN were found in 4 neonates in hyperammonemic coma (QUIN range, 250–990 nM; control mean, 110 ± 90 nM; p < 0.005). Similar elevations of neopterin were found (range, 24–75 nM; control mean, 9.0 ± 4.9 nM; p < 0.005). In addition, significant elevations of QUIN were found in 14 older children with congenital hyperammonemia (mean, 50 ± 20 vs 17 ± 6 nM; p < 0.05). Neopterin levels were not elevated in these children. The QUIN may originate from an increase in tryptophan transport across the blood-brain barrier or from induction of indolamine-2,3-dioxygenase activity. These findings support a role for QUIN in the neuropathology of congenital hyperammonemia. They also suggest the potential utility of N-methyl-D -aspartate receptor–-blocking agents or inhibitors of QUIN synthesis in the treatment of hyperammonemic coma. |
